Significant improvements in the primary success rate of various medical and surgical treatments of atherosclerotic disease have been made in the last few years. Yet recurring failures continue in 30 to 50% of the individuals after balloon angioplasty, bypass surgery, and endarectomy due to late restenosis of the treated vessel. The restenosis is a result of a complex series of fibroproliferative responses to the vascular injury that results in vascular smooth muscle cell proliferation, migration and neointimal accumulation, and secretion of extracellular proteins. Microtubules are likely involved in controlling or moderating critical intracellular mechanisms necessary for the vascular smooth muscle cells fibroproliferative response. We found that taxol, an anti-tumor drug which stabilizes microtubules, inhibited vascular smooth muscle cell proliferation, migration, and invasion in vitro. In vivo, taxol prevented the neointimal vascular smooth muscle cell accumulation in the rat carotid artery after balloon dilation and endothelial denudation injury. These experiments suggest that taxol or other pharmacologic agents that stabilize microtubules may have therapeutic value in preventing human restenosis after balloon angioplasty, bypass surgery, or endarectomy.